Murine norovirus 1 (MNV1) replication induces translational control of the host by regulating eIF4E activity during infection

J Biol Chem. 2015 Feb 20;290(8):4748-58. doi: 10.1074/jbc.M114.602649. Epub 2015 Jan 5.

Abstract

Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.

Keywords: Eukaryotic Translation Initiation Factor 4E (eIF4E); Host-Pathogen Interaction; Mitogen-activated Protein Kinase (MAPK); Protein Synthesis; RNA Virus; Translation Control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caliciviridae Infections / genetics
  • Caliciviridae Infections / metabolism*
  • Cats
  • Cell Line
  • Eukaryotic Initiation Factor-4E / genetics
  • Eukaryotic Initiation Factor-4E / metabolism*
  • Host-Pathogen Interactions*
  • Humans
  • Mice
  • Norovirus / physiology*
  • Phosphorylation / genetics
  • Polyribosomes / genetics
  • Polyribosomes / metabolism
  • Protein Biosynthesis*
  • Protein Transport / genetics
  • Viral Proteins / biosynthesis*
  • Viral Proteins / genetics
  • Virus Replication / physiology*

Substances

  • Eukaryotic Initiation Factor-4E
  • Viral Proteins